Cerebellar DBS in SCA1 and SCA3 Study
Deep Brain Stimulation of the Deep Cerebellar Nuclei in Subjects With Spinocerebellar Ataxia: A Safety and Feasibility Study
The purpose of this study is to evaluate the safety and feasibility of deep brain stimulation (DBS) in the deep cerebellar nuclei (DCN) in patients with Spinocerebellar Ataxia (SCA) types 1 and 3.
Primary Objective: The incidence and nature of treatment-related adverse events across the entire study, including serious treatment-related adverse events such as intracerebral hemorrhage, infection, and serious or unanticipated adverse device effects (SADEs and UADEs).
Secondary/Exploratory Objectives:
- Evaluation of the effect of Dentate Nucleus (DN) - Deep Brain Stimulation (DBS). Ataxia severity will be quantified using the Scale of Assessment and Rating of Ataxia (SARA), Patient-Reported Outcome Measure of Ataxia (PROM-Ataxia), and kinematics.
- To characterize electrophysiological activity across the cerebellothalamocorticomuscular (CTCM) network at rest and during motor behaviors.
- To examine how DN-DBS modulates oscillatory activity and coupling across the CTCM circuit in relation to improvements in controlling ataxia.
調査の概要
状態
詳細な説明
People with spinocerebellar ataxia (SCA) face progressively disabling symptoms such as poor balance, frequent falls, and a loss of muscle control. Currently, there are no approved treatments for these symptoms.
Developing medications to treat SCA is incredibly difficult because the brain's movement center-the cerebellum-has complex, damaged wiring that varies between patients. However, all signals from this complex brain region flow through a single exit point called the deep cerebellar nuclei (DCN). This makes the DCN (specifically, the dentate nucleus or DN) a perfect target for brain stimulation. Over the past five years, animal studies have shown that using a device to stimulate this area (called deep brain stimulation, or DBS) can significantly improve movement control. Recently, a small study showed promising early results in humans, particularly in two patients with SCA type 3.
To translate these findings into a standard treatment that has the potential to improve patients' lives, the investigators must first determine whether this is feasible and safe. The investigators will also need to see if this treatment works for different types of SCA, since cerebellar damage varies from person to person. Therefore, the aim of this study is to test and safety, feasibility, and early effectiveness of DBS on both sides of the brain in 12 people with SCA types 1 and 3. During the study, the investigators will use temporary external wires and a brain-recording device to listen to the brain's signals. By matching these signals with standard brain wave tests (EEGs), the investigators will hopefully understand exactly how this stimulation fixes the brain's movement network.
研究の種類
入学 (推定)
段階
- 適用できない
連絡先と場所
研究連絡先
- 名前：Natasha Desai
- 電話番号：347-882-4315
- メール：nd2528@cumc.columbia.edu
研究連絡先のバックアップ
- 名前：Gordon Baltuch, MD, PhD
- メール：gb2774@cumc.columbia.edu
研究場所
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New York
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New York、New York、アメリカ、10032
- Columbia University Irving Medical Center
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コンタクト：
- Natasha Desai
- 電話番号：347-882-4315
- メール：nd2528@cumc.columbia.edu
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コンタクト：
- Nadia Amokrane
- 電話番号：347-882-4315
- メール：na2855@cumc.columbia.edu
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主任研究者：
- Gordon Baltuch, MD
-
副調査官：
- Sheng-Han Kuo, MD
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Ohio
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Cleveland、Ohio、アメリカ、44195
- Cleveland Clinic
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コンタクト：
- Jeffrey Negrey
- 電話番号：216-316-6896
- メール：negreyj2@ccf.org
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主任研究者：
- Andre Machado, MD
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副調査官：
- Kenneth Baker, PhD
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-
参加基準
適格基準
就学可能な年齢
- 大人
健康ボランティアの受け入れ
説明
Inclusion Criteria:
- Subject is aged >= 18 years and =< 60 years.
- Subject has moderate ataxia severity, as demonstrated by a Scale for Ataxia Rating and Assessment (SARA) score >= 11.
- Subject has genetic confirmation of pathological repeat expansions in ATXN1 (for SCA1, repeat size >= 40) and ATXN3 (for SCA3, repeat size >= 56).
- Subject has been on a stable and optimized standard of care (SoC) regimen for at least 3 months prior to Screening (including physical therapy) and continues to exhibit signs of cerebellar ataxia.
- Subject has a minimum 6th grade reading level, as determined by the Rapid Estimate of Adult Literacy in Medicine (REALM) scale.
- Subject is able and willing to give informed consent and attend all study visits.
- Subject is available for all follow-up visits during the length of the study.
Exclusion Criteria:
- Subject is unable to provide informed consent.
- Subject has presence of overt tremor, dystonia, and/or parkinsonism, which are atypical features and could be suggestive of prominent extra-cerebellar circuit involvement that may not respond well to cerebellar DBS.
- Subject is wheelchair dependent and may be too progressed to complete gait assessments.
- Subject is unable to stop anticoagulation or platelet anti-aggregation therapy for study procedures.
- Subject has a Montreal Cognitive Assessment (MoCA) score =< 24.
- Subject has a diagnosis of epilepsy.
- Subject has a major active psychiatric illness that may interfere with the study, such as psychiatric disorders or severe personality disorders.
- Subject has an untreated or inadequately treated major depressive episode.
- Subject is pregnant, lactating, or planning to become pregnant during the study.
- For women of childbearing potential, subject is unable or unwilling to use accepted contraception methods.
- Subject is unable to communicate with investigators or staff.
- Subject has contraindications to DN DBS, including significant small vessel ischemic disease, vertebrobasilar vascular disease, and/or any other structural abnormalities of the cerebellum, cerebellar peduncles, and brain stem that would preclude safe placement of the DBS leads.
- Subject has contraindications to magnetic resonance (MR) imaging, e.g., weight incompatible with scanner, implanted metallic devices or electrical devices (pacemaker, defibrillator, spinal cord stimulator), or intolerance to MRI contrast agents.
- Subject is enrolled in another device, biologic or pharmaceutical study within 30 days of consent in the current study (i.e., patients cannot be enrolled if participation in another study was not completed at least 30 days prior to consent).
- Subject has evidence of behavior(s) consistent with alcohol or substance abuse/dependence within the preceding 6 months, as outlined by the DSM-V criteria.
- Subject has a condition that, in the opinion of the investigator, would significantly increase the risk for interference with study compliance, safety, or outcome.
- Subject is at risk for suicide, defined by a total score >= 3 on the Columbia Suicide Severity Rating Scale (C-SSRS).
- Patients who are not able to read, speak and/or understand English.
研究計画
研究はどのように設計されていますか？
デザインの詳細
- 主な目的：処理
- 割り当て：なし
- 介入モデル：単一グループの割り当て
- マスキング：なし（オープンラベル）
武器と介入
参加者グループ / アーム |
介入・治療 |
|---|---|
|
実験的：DBS Intervention
Participants will undergo surgical implantation of the DBS leads, followed by a second surgery to implant a pulse generator (IPG) which generates electricity.
|
The UG3NS140720 Deep Brain Stimulation System is primarily comprised of components from the Medtronic Percept™ system, which is approved in the U.S. by the FDA for unilateral or bilateral stimulation of the ventral intermediate nucleus (VIM) of the thalamus as adjunctive therapy for ET, cerebellar outflow tremor, and MS-related tremor. This system is also approved to be used on patients with neurologic disorders such as Parkinson's disease, dystonia, or epilepsy. The FDA has not approved any DBS system for the stimulation of the Deep Cerebellar Nuclei (DCN) for this patient population. Deep brain stimulation (DBS) utilizes surgically implanted electrodes and a neurostimulator to deliver electrical energy to specific targeted structures deep within either one or both hemispheres of the brain.
他の名前：
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この研究は何を測定していますか？
主要な結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Incidence of treatment-related adverse events
時間枠：Up to 72 months
|
To further understand the safety and optimize a novel therapeutic target to achieve ataxia control for individuals with SCA.
The adverse events will be evaluated and tallied if they met the criteria as Serious Adverse Events (SAE), Serious Adverse Device Effects (SADE), and Unanticipated (Serious) Adverse Device Effects (UADE).
|
Up to 72 months
|
二次結果の測定
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
|
Mean Scale for Assessing and Rating of Ataxia (SARA) Score
時間枠：Baseline, Month 11
|
To characterize the effect of DN-DBS on disease-related impairments, the study will measure ataxia severity as assessed by the Scale for Assessing and Rating of Ataxia (SARA).
SARA is a clinical scale that includes 8 different domains of neurological exams, including gait, stance, sitting, speech, and hand dexterity.
The total amount of points on SARA ranges from 0 (no ataxia) to 40 (most severe ataxia).
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Baseline, Month 11
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Mean Patient-Reported Outcome Measures - Ataxia (PROM-Ataxia) Scale Score
時間枠：Baseline, Month 11
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To characterize the effect of DN DBS on ataxia severity and related cognitive and emotional symptoms in SCA, the study will utilize the Patient-Reported Outcome Measures - Ataxia (PROM-Ataxia) scale.
PROM-Ataxia is a 3-domain, 70-item questionnaire which assesses the impact of cerebellar dysfunction on physical abilities, activities of daily living, and cognitive-emotional challenges.
The maximum severity score on PROM-Ataxia is 280, where all 70 questions are scored on a 0-4 Likert scale.
0 represents never and 4 represents always.
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Baseline, Month 11
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Mean Cerebellar Cognitive Affective Syndrome Scale (CCAS) Score
時間枠：Baseline, Month 11
|
SCA patients may have cognitive impairment, presumed to come from the dysfunctional cerebellum.
Therefore, cognition status will be measured by the Cerebellar Cognitive Affective Syndrome Scale (CCAS).
The CCAS evaluates multiple cognitive domains such as executive function, attention, memory, language, visual-spatial skills, abstract reasoning, and neuropsychiatric features.
The total possible score is 120 points; the Pass / Fail measure provides a maximum fail score of 10 (i.e., 10 failed tests).
A fail score of 0 is normal.
In a patient with cerebellar disease, a fail score of 1 indicates Possible CCAS, a fail score of 2 indicates Probable CCAS, and a fail score of 3 or more indicates Definite CCAS.
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Baseline, Month 11
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Mean Patient Health Questionnaire (PHQ-9) Score
時間枠：Baseline, Month 11
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To assess depression symptoms, the Patient Health Questionnaire assessment will be used.
The PHQ is a 9-item patient-reported assessment which asks how often a patient has experienced a symptom in the prior 2 weeks.
Responses range from "0" (Not at all) to "3" (nearly every day).
Scores range from 0 to 27, with total scores over 10 indicating a presence of depression.
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Baseline, Month 11
|
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Mean Generalized Anxiety Disorder (GAD) Scale Score
時間枠：Baseline, Month 11
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To assess anxiety symptoms, the GAD scale will be used.
The Generalized Anxiety Disorder (GAD) scale is a 7-item patient-reported assessment which assesses how often a patient has experienced a symptom of anxiety in the last 2 weeks.
To assess depression symptoms, the Patient Health Questionnaire assessment will be used.
Responses range from "0" (Not at all) to "3" (nearly every day).
Scores range from 0 to 21, with total scores over 10 indicating a presence of anxiety.
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Baseline, Month 11
|
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Mean Patient Global Impression (PGI) Score
時間枠：Baseline, Month 11
|
The Patient Global Impression (PGI) scores are single-item patient-reported assessments.
This study will use the severity (PGI-S) and change (PGI-C) scores.
|
Baseline, Month 11
|
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Mean Gait Measure of Ataxia
時間枠：Baseline, Month 11
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Kinematic measures of ataxia will be measured by 6 wearable sensors from the APDM Mobility Lab System.
The system has recently been validated to track cerebellar ataxia severity in SCA patients.
SCA patients have increased postural sway, increased toe-out angle variability, and increased double-support time variability.
APDM sensors will also be used to study different gait cycles and finger-to-target movements as indicators for gait and hand ataxia, respectively.
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Baseline, Month 11
|
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Mean Postural Kinematic Measure of Ataxia
時間枠：Baseline, Month 11
|
Kinematic measures of ataxia will be measured by 6 wearable sensors from the APDM Mobility Lab System.
The system has recently been validated to track cerebellar ataxia severity in SCA patients.
SCA patients have increased postural sway, increased toe-out angle variability, and increased double-support time variability.
APDM sensors will also be used to study different gait cycles and finger-to-target movements as indicators for gait and hand ataxia, respectively.
|
Baseline, Month 11
|
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Mean EQ-5D-3L Score
時間枠：Baseline, Month 11
|
The EQ-5D-3L is a self-assessed, health related, quality of life questionnaire.
The scale measures quality of life on a 5-component scale including mobility, self-care, usual activities, pain/discomfort, and anxiety/depression.
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Baseline, Month 11
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その他の成果指標
結果測定 |
メジャーの説明 |
時間枠 |
|---|---|---|
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Number of evaluable recordings completed by participants
時間枠：From Implant to End of Study (Approximately 11 Months)
|
EEG, EMG, and LFP recordings will be collected at rest and during ataxia-eliciting behaviors at specified study visits to characterize activity, as well as assess how DN-DBS modulates oscillatory activity and coupling, across the cerebellothalamocorticomuscular (CTCM) network.
|
From Implant to End of Study (Approximately 11 Months)
|
協力者と研究者
スポンサー
捜査官
- 主任研究者：Gordon Baltuch, MD、CUIMC
- スタディディレクター：Sheng-Han Kuo, MD、CUIMC
研究記録日
主要日程の研究
研究開始 (推定)
一次修了 (推定)
研究の完了 (推定)
試験登録日
最初に提出
QC基準を満たした最初の提出物
最初の投稿 (実際)
学習記録の更新
投稿された最後の更新 (実際)
QC基準を満たした最後の更新が送信されました
最終確認日
詳しくは
本研究に関する用語
その他の研究ID番号
- ACYY0046
- 1UG3NS140720-01 (米国 NIH グラント/契約)
個々の参加者データ (IPD) の計画
個々の参加者データ (IPD) を共有する予定はありますか?
医薬品およびデバイス情報、研究文書
米国FDA規制医薬品の研究
米国FDA規制機器製品の研究
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